Sepsis is the name given to infection when symptoms of inflammatory response are present. Of patients hospitalized in an intensive care unit (ICU) who have an infection, 82% have sepsis. Sepsis is defined as an infection-induced syndrome involving two or more of the following features of systemic inflammation: fever or hypothermia, leukocytosis or leukopenia, tachycardia, and tachypnea or a supranormal minute ventilation. Sepsis may be defined by the presence of any of the following ICD-9-CM codes: 038 (septicemia), 020.0 (septicemic), 790.7 (bacteremia), 117.9 (disseminated fungal infection), 112.5 (disseminated Candida infection), and 112.81 (disseminated fungal endocarditis).
Sepsis is diagnosed either by clinical criteria or by culture of microorganisms from the blood of patients suspected of having sepsis plus the presence of features of systemic inflammation. Culturing some microorganisms can be tedious and time-consuming, and may provide a high rate of false negatives. Bloodstream infection is diagnosed by identification of microorganisms in blood specimens from a patient suspected of having sepsis after 24 to 72 hours of laboratory culture. Currently, gram-positive bacteria account for 52% of cases of sepsis, gram-negative bacteria account for 38%, polymicrobial infections for 5%, anaerobes for 1%, and fungi for 5%. For each class of infection listed, there are several different types of microorganisms that can cause sepsis. The high rate of false negative microbiologic cultures leads frequently today to empiric treatment for sepsis in the absence of definitive diagnosis. Infection at many different sites can result in sepsis. The most common sites of infection in patients with sepsis are lung, gut, urinary tract, and primary blood stream site of infection. Since sepsis can be caused by many infection with microorganisms at many different sites, sepsis is a very heterogeneous disease. The heterogeneity of sepsis increases the difficulty in devising a diagnostic test
The number of patients with sepsis per year is increasing at 13.7% per year, and was 659,935 in 2000. The incidence of sepsis in the United States in 2000 was 240.4 cases per 100,000 population. Sepsis accounted for 1.3% of all hospitalizations in the U.S. from 1979 to 2000. During this period, there were 750 million hospitalizations in the U.S. and 10.5 million reported cases of sepsis.
Sepsis is the leading cause of death in critically ill patients, the second leading cause of death among patients in non-coronary intensive care units (ICUs), and the tenth leading cause of death overall in the United States. Overall mortality rates for sepsis are 18%. In-hospital deaths related to sepsis were 120,491 (43.9 per 100,000 population) in 2000.
Care of patients with sepsis is expensive and accounts for $17 billion annually in the United States alone. Sepsis is often lethal, killing 20 to 50 percent of severely affected patients. Furthermore, sepsis substantially reduces the quality of life of those who survive: only 56% of patients surviving sepsis are discharged home; 32% are discharged to other health care facilities (i.e., rehabilitation centers or other long-term care facilities), accruing additional costs of care.
Cost of care, morbidity and mortality related to sepsis are largely associated with delayed diagnosis and specific treatment of sepsis and the causal infection. Early diagnosis of sepsis is expected to result in decreased morbidity, mortality and cost of care. The average length of hospital stay in patients with sepsis is twelve days.
Severe sepsis is defined as sepsis associated with acute organ dysfunction. The proportion of patients with sepsis who had any organ failure is 34%, resulting in the identification of 256,033 cases of severe sepsis in 2000. Organ failure had a cumulative effect on mortality: approximately 15% of patients without organ failure died, whereas 70% of patients with 3 or more failing organs (classified as having severe sepsis and septic shock) died. Risk of death from sepsis increases with increasing severity of sepsis. Currently determination of the severity of sepsis and determination of whether, in a patient with sepsis, the sepsis is increasing or decreasing in severity, is based upon clinical events such as failing organs. Determination that, in a patient with sepsis, the sepsis is increasing in severity, may allow more intensive therapy to be given which may increase the likelihood of the patient surviving. The availability of a diagnostic test that would allow monitoring of patients with sepsis to determine whether the sepsis is increasing or decreasing in severity may allow early detection of deterioration and earlier intensification of therapy and less risk of death or disability.
Sepsis results either from community-acquired infections or hospital-acquired infections. Sepsis occurs in 1.3% of all U.S. hospitalizations. Hospital-acquired infections are a major source of sepsis, accounting for 65% of sepsis patients who are admitted to an intensive care unit. Sepsis is a major cause of admission to a hospital intensive care unit. 23-30% of patients admitted to an intensive care unit for longer than 24 hours will develop sepsis. Sepsis is a common complication of prolonged stay in an ICU. 8% of patients who remain in an ICU for longer than 24 hours will develop sepsis.
There is a need for screening diagnostic tests for sepsis and for tests to monitor sepsis severity with relatively few false negatives and high sensitivity and specificity.